Interferon continues to get a bad rap...

[geterdone]

I am in the view now that interferon had been getting a bad rap for the long term post treatment side effects. It would seem to me that the ribavirin stays in your system long after the interferon has been degraded and dismantled by the body. I would think that it would explain the fatigue 6 months / one year post treatment, any thoughts?


Source of information / http://en.wikipedia.org/wiki/Ribavirin

Ribavirin is absorbed from the GI tract probably by nucleoside transporters. Absorption is about 45%, and this is modestly increased (to about 75%) by a fatty meal. Once in the plasma, ribavirin is transported through the cell membrane also by nucleoside transporters.

Ribavirin is widely distributed in all tissues, including the CSF and brain.

* Distributed to ALL tissues*

The pharmacokinetics of ribavirin is dominated by trapping of the phosphated form inside cells, particularly red blood cells

* Trapping it inside the Red Blood Cell*

The volume of distribution of ribavirin is large (2000 L/kg) and the length of time the drug is trapped varies greatly from tissue to tissue.

* Varies from tissue to tissue* // I am assuming they are also taking into account of organs also.

The mean half-life for multiple doses in the body is about 12 days,

* Half-Life 12 days*

Very long-term kinetics are dominated by the kinetics of RBCs (half-life 40 days).

* RBCs half-life 40 days*

RBCs store ribavirin for the lifetime of the cells, releasing it into the body's systems when old cells are degraded in the spleen.

* RBC holds ribavirin for a life time*

* RELEASING IT INTO THE BODY”S SYSTEMS WHEN THE OLD CELLS ARE
   DEGRADED IN THE SPLEEN* ?

Optimum word here is released into the body’s systems. So is it able to in-bed it self into a new red blood cell after the old has been degraded????


jasper

[merryBe]

I think the INF boost in general can put us at a disadvantage in the lower levers once pulled. This not only explains the rates of releaspse, if tx is stopped abruptly and the spleen does not get caught up in time, but even if one does manage to SVR you still have the overall toll AND the fact that as we age our immune systems wear out...out bone marrow is also heavily taxed during the long chemo...

then to this you add evidence that Riba in one study lower the normal ratio of regular DNA to midochondril, from 200-1 down to 30-1.
That means a reduction of 90% or more of RNA?DNA and that means a lot of messed up weak cells.
I shouldn't be surprised if it would take some time to regain ones health, nor that say a 30 year old who bounces back would as unuseual as a 60 yr old doing it.

the body takes 7 yrs to replace all our types of tissiue with new healthy cells, only the liver does this in under 2 years....the rest takes time.

mb..

[orleans]

I don't know enough to comment, but this ONE thing I do know---Life without RIBA is livable even if INF is continued. I stopped the Riba 2/2, continuing INF/Alinia and things have improved dramaticly. Still a little tired and fuzzy but no longer bed ridden. jerry

[Max60]

I, too, am interested in the most perplexing post tx sfx?

For me it's the cholesterol rise/hypometabolic 'stuff'

[jmjm530]

What riba sfx are you referring to "most perplexing"?

As to how fast riba gets flushed from the system, someone once laid out a mathematical formula where the six month period came from and its basis was ribavirin's long  half life.

Not sure if that is how they come up with the six month figure or perhaps it's simply based on clinical evidence by finding minute traces of ribvirin in plasma for as long as six months treatment. That would be the acid test wouldn't it -- if they find minute traces of riba in plasma for a six month window then it's there and should trump any theory, and I believe that they've found it.

-- Jim

[geterdone]

Yes, I partly understand the interferon and ribavirin and the similarity but also separate side effects and one being fatigue and the ribavirins association with anemia and one of the most perplexing post TX side effects and am trying to point out why this may be happening but am not sure if it is correct.

Also following that thought, if the RBC half life is 40 days and in that 40 days the ribavirin is also on a declining percentage scale of 12 days would it not still be entering new red blood cells as the ribavirin is declining even in its most minute amount. So, if the last tractable amount of ribavirin by laboratory standards was still is in your system would it not be 40 days before the untraceable amounts (excluding tissues) be completely out, or is it?, ribavirin does not live and is a synthetic drug and lays in the tissues until moved and when it does by blood or plasma, would it not seek out the red blood cells?

[jmjm530]

I'm not saying that riba is a lovely drug and does not have lingering side effects -- just that interferon has a known physical effect on the immune system and has been associated with depression even when used without ribavirin as with some cancer patients. I suppose you could research out the side effects of riba monotherapy and compare it to interferon monotherapy and draw some conclusions that way as well.

[geterdone]

Understand, BUT forget the pregnancy; this is telling me that the ribavirin is trapped inside of the red blood cells for the life time of the cell and when its life is over the cell is degraded by the spleen and in doing so the ribavirin escapes (or is unable to be degraded fully by the spleen) and then is released back into the body to find a newly produced red blood cell, or am I missing something? Another thing I am curious about is if the ribavirin enters tissues, brain etc. could also not be picked up on the blood test markers for symptoms because of the low detection of it over time?

jasper

[jmjm530]

I'm not familiar if haploid cells are affected, but the literature always mentions the long-half life of ribavirin as the reason to wait.
--------------------------------


"...Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple dose half-life of 12 days, and it may persist in non-plasma compartments for as long as 6 months. Ribavirin therapy is contraindicated in women who are pregnant and in the male partners of women who are pregnant..."

http://www.druglib.com/druginfo/ribavirin/warnings_precautions/

[desrt]

Beg to differ. On my way out the door right now, but will look up reference later. It's damaged haploid cells that need to be cleared, not actual presence of riba.

[geterdone]

I’m thinking it is far beyond the pregnancy stage if I am reading this explanation correctly and that is not to say I am and is why I had posted it.
jasper

[jmjm530]

The reason is because many of the physical problems described post treatment are immune-related and it's the interferon that ramps up the immune system. Interferon is also implicated in psychological problems such as depression per the literature.

Ribavirin is tetragenic meaning it can cause birth defects. So from what I've read it's not that ribavirn damages the reproductive system but that minute amounts of the tetragen may be around for as much as six months, given ribavirin's long half life.

-- Jim

[desrt]

It's not so much the half-life of these drugs, but rather the damage that they do. The reason you use birth control for six months after tx is not that the riba (an RNA mutagen) is still around, but rather the damage done to your reproductive system takes that long to clear.